Well-known indicia of cardiovascular risk include age, sex, smoking, systolic blood pressure and total cholesterol. In addition, several biochemical markers of cardiovascular health risk have been proposed, including C-reactive protein (CRP; Schishehbor et al., Cleve Clin J. Med. 2003 70, 634-40), B-type natriuretic peptide (BNP; Silver et al., Congest Heart Fail 2003 9,127-32), sialic acid (Crook et al., 1998 Clin Sci 95, 53-57), etc. For a review of several biochemical markers in the management of coronary artery disease, see Rosenson, et al. Am J Cardiol. 2003 92,10i-8i.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine/hormone that has been associated with a number of disease states. MIF expression has been suggested to correlate with diseases like sepsis (Lehmann et al., 2001 Intensive Care Med 27,1412-5), prostate cancer (Meyer-Siegler et al., 2002 Cancer 94, 1449-56; Hudson et al., U.S. Pat. No. 6,043,044), aneurysmal expansion (Pan et al., 2003 J Vasc Surg 37, 628-35), acute myocardial infarction (Yu et al., 2001 Am J Card 88, 774-7), atherosclerosis (Burger-Kentischer, 2002 Circulation 105, 1561-66), diabetes (Sakaue et al., 1999 Mol Med. 5, 361-71), etc., and bypass surgery (Gando et al., 2000 Surg Today 30, 689-94). For a review of pathophysiological aspects of macrophage migration inhibitory factor, see Nishihira, 1998 Int J Mol Med. 2, 17-28.
We have determined that the serum level of MIF is extremely elevated in patients with high cardiovascular risk, and that it falls rapidly when interventions are made which reduce this risk. Prior to our work, MIF levels have never been associated with cardiovascular risk in non-diseased or non-diagnosed persons. Like CRP, MIF is a marker of cardiovascular risk providing clinically important prognostic information in the assessment of overall cardiovascular risk.